A Description of Celiac Disease and How to Protect Children

I have a family member who suffered from this disease for a long time until he found out what was wrong. Now he eats a gluten-free diet and is feeling great – shout out to him! I though it would be nice to write about this disease because it might help any parents out there make smart choices for their babies. So without further ado, here you have my first post:

Celiac disease (CD) is a permanent auto-immune disease that occurs in some genetically predisposed individuals when they ingest gluten, a protein found in the grains wheat, rye, and barley. When individuals suffering from CD ingest gluten, their immune system attacks their intestines and causes lesions. Sufferers of the disease experience gastrointestinal symptoms such as abdominal pain, diarrhea, flatulence, and constipation. The damage done to the intestines often leads to the inability to properly absorb nutrients, which causes other symptoms such as anemia, weight loss, and osteoporosis.¹

To understand the mechanisms that cause CD and how it is diagnosed, it helps to understand some relevant microbiology. The major histocompatibility complex (MHC) is a part of our genome that allows our immune system to function properly. Within the MHC, there are human leukocyte antigen (HLA) genes which are used to synthesize specific proteins. The proteins made using these HLA genes are located on the outermost surface of our cells, the cell membrane. They are used to display markers that our immune system recognizes as belonging to our own healthy cells. These markers are called “self” antigens. When our immune system recognizes self antigens, it does no harm to the cells displaying them. However, when a cell is infected by a harmful microorganism, the proteins made using HLA genes allow the cell to display pieces of that microorganism on the cell membrane. These “non-self” antigens prompt the immune system to kill the microorganism within the infected cell, and the infected cell itself is consequently killed as a sort of collateral damage.

Expression of HLA genes varies tremendously within the human population, and the proteins produced using HLA genes are unique to every individual. There are two specific HLA genes that predispose people for CD: DQ2 and DQ8.⁴ Only one of these genes needs to be expressed for an individual to be predisposed to CD. From these genes, cells produce proteins which can display gluten to the immune system. Of course, gluten is not a naturally occurring protein within our bodies, so the immune system will recognize it as non-self and attack the cells (specifically, the intestinal cells).

Here's an animation I made for the visual learners out there...



When a person ingests food, the food moves from the mouth into the esophagus. No digestion or absorption takes place as the food passes quickly through the esophagus into the stomach. The stomach, used for digesting and churning food, is a very strong, muscular organ with relatively thick walls. Almost no nutrients get absorbed into the body through the stomach. After exiting the stomach, the partially digested food enters the duodenum, the uppermost section of our intestines where nutrient absorption begins. In a person with active HLA DQ2 or DQ8 genes, ingested gluten can be absorbed and presented to the immune system, causing damage to the intestines as described above.

Thus, three sources of evidence for diagnosing CD are:
1) Considering of the patients’ symptoms
2) Testing patients for the expression of HLA DQ2 and DQ8
3) Using a biopsy of the duodenum to check for damage to the intestines

As it turns out, however, only 4% of patients who express either the DQ2 or DQ8 gene actually develop CD.³ Scientists believe this is because there are additional genetic and environmental factors necessary for the disease to manifest itself. There are currently about 7 other genes being examined for the role they play in CD development.

Two possible environmental factors that might play a role in the development of the disease are the timing of gluten introduction to the diet and breast feeding patterns. One study, known as the DAISY experiment, suggests that 4-6 months of age is the optimal window of time to first feed a child food containing gluten so as to decrease the child’s chance of suffering from CD later in life.³ However, this study does not address the amount of gluten the child should be fed. Another study took on this issue and found that during an era when children were fed food containing high levels of gluten during weaning, 4 times as many children developed CD compared to past incidence.² Additionally, multiple studies support the notion that breastfeeding, particularly at the time of gluten introduction to the diet, significantly reduces a child’s chance of developing CD.³

The only known effective treatment for the disease is the complete avoidance of food containing gluten. Current research is aimed at using food grade enzymes to break down accidentally ingested gluten,⁵ and additional research may lead to the ability to use gene therapy to combat the negative effects that the expression of DQ2 and DQ8 facilitate. Until another treatment (or cure) is found, CD patients should avoid products made with wheat, rye, and barley, and parents should introduce gluten slowly into their child’s diet at 4-6 months of age, while the child’s mother continues to breastfeed him or her.

Thanks for reading, and if you have any questions, don’t be shy about asking me! I’ll do my best to help get them answered.

References:
[1] Gray AM and Papanicolas IN. “Impact of symptoms on quality of life before and after diagnosis of coeliac disease: results from a UK population survey.” BMC Health Services Research 10.105 (2010): [Epub ahead of print]. Web.

[2] Olsson C, Hernell O, Hörnell A, Lönnberg G, Ivarsson A. “Difference in celiac disease risk between Swedish birth cohorts suggests an opportunity for primary prevention.” Pediatrics 122.3 (2008): 528-534. Web.

[3] Silano M, Agostoni C, and Guandalini S. "Effect of the Timing of Gluten Introduction on the Development of Celiac Disease." World Journal of Gastroenterology 16.16 (2010): 1939-942. Web.

[4] Verdu EF, Huang X, Natividad J, Lu J, Blennerhassett PA, David CS, McKay DM, Murray JA. “Gliadin-Dependent Neuromuscular and Epithelial Secretory Responses in Gluten-Sensitive HLA-DQ8 Transgenic Mice.” AJP - Gastrointestinal and Liver Physiology 294.1 (2008): G217-225. Web.

[5] Ehren J, Morón B, Martin E, Bethune MT, Gray GM, Khosla C. “A food-grade enzyme preparation with modest gluten detoxification properties.” PLoS One 4:7 (2009): e6313. Web.